| Full gene name: | Bloom syndrome, RecQ helicase-like |
|---|---|
| Entrez Gene ID: | 641 |
| Location: | 15q26.1 |
| Synonyms: | RECQ2, RECQL2, RECQL3, BS |
| Type: | protein-coding |
SNPs given by the user that are near or inside this gene:
| SNP | Distance (bp) | Direction |
|---|---|---|
| rs8042680 | 162651 | downstream |
The Bloom syndrome gene product is related to the RecQ subset of DExH box-containing DNA helicases and has both DNA-stimulated ATPase and ATP-dependent DNA helicase activities. Mutations causing Bloom syndrome delete or alter helicase motifs and may disable the 3’-5’ helicase activity. The normal protein may act to suppress inappropriate recombination. [provided by RefSeq, Jul 2008]
| OMIM ID: | `OMIM ID 604610 `_ |
|---|
Allelic Variants (Selected Examples)
.0001 BLOOM SYNDROME
In 4 ostensibly unrelated persons of Jewish ancestry with Bloom syndrome (210900), Ellis et al. (1995) found homozygosity for a 6-bp deletion/7-bp insertion at nucleotide 2281 of the BLM cDNA. Deletion of ATCTGA and insertion of TAGATTC caused the insertion of the novel codons for LDSR after amino acid 736, and after these codons there was a stop codon. Ellis et al. (1995) concluded that a person carrying this deletion/insertion mutation was a founder of the Ashkenazi-Jewish population, and that nearly all Ashkenazi Jews with Bloom syndrome inherited the mutation identical by descent from this common ancestor. Identification of the mutation by a PCR test was now possible for screening for carriers among Ashkenazim.
Straughen et al. (1998) described a rapid method for detecting the 6-bp deletion/7-bp insertion, a predominant Ashkenazi Jewish mutation in Bloom syndrome. They commented that in the Bloom syndrome registry, one or both parents of 52 of the 168 registered persons are Ashkenazi Jews.
Using a convenient PCR assay, Ellis et al. (1998) found the 6-bp del/7-bp ins mutation, blm(Ash), on 58 of 60 chromosomes transmitted by Ashkenazi parents to persons with Bloom syndrome. In contrast, in 91 unrelated non-Ashkenazic persons with BS whom they examined, blm(Ash) was identified in only 5, these coming from Spanish-speaking Christian families from the southwestern United States, Mexico, or El Salvador. These data, along with haplotype analyses, showed that blm(Ash) was independently established through a founder effect in Ashkenazi Jews and in immigrants to formerly Spanish colonies. This striking observation underscored the complexity of Jewish history and demonstrated the importance of migration and genetic drift in the formation of human populations.
In a study of the frequency of the BLM 6-bp del/7-bp ins mutation in a group of Ashkenazi Jews, unselected for personal or family history of Bloom syndrome, Oddoux et al. (1999) found the mutation in 5 of 1,155 individuals, yielding a frequency of 1/231 (95% CI, 1/123-1/1,848). The low frequency is consistent with an absence of heterozygote advantage for carriers of 1 copy of the mutant allele. The frequency of heterozygotes for other autosomal recessive conditions within their panel had been validated in other studies, suggesting that the test panel was representative of the Ashkenazi Jewish population. Those frequencies were Tay-Sachs disease, 1/28; cystic fibrosis, 1/25; Gaucher disease, 1/15; BRCA2, 6174delT, 1/106; Canavan disease, 1/41; and Fanconi anemia complementation group C, 1/116.
To determine whether carriers of BLM mutations are at increased risk of colorectal cancer, Gruber et al. (2002) genotyped 1,244 cases of colorectal cancer and 1,839 controls, both of Ashkenazi Jewish ancestry, to estimate the relative risk of colorectal cancer among carriers of the BLM(Ash) founder mutation. Ashkenazi Jews with colorectal cancer were more than twice as likely to carry the BLM(Ash) mutation than Ashkenazi Jewish controls without colorectal cancer (odds ratio = 2.45, 95% CI 1.3 to 4.8; P = 0.0065). Gruber et al. (2002) verified that the APC I1307K mutation (611731.0029) did not confound their results.
.0002 BLOOM SYNDROME
In a Japanese patient with Bloom syndrome (210900), Ellis et al. (1995) found homozygosity for a deletion of CAA at nucleotide position 631-633, resulting in a stop codon at amino acid position 186.
.0003 BLOOM SYNDROME
In an Italian patient (BSR92) with Bloom syndrome (210900), German et al. (2007) identified homozygosity for a large deletion in exons 11 and 12 in the RECQL3 gene (2308-953_2555+4719del6126), causing a frameshift (ile770fs). (German and Ellis (2001) noted that the mutation in patient BSR92 was assigned incorrectly by Ellis et al. (1995). Ellis et al. (1995) had reported the patient to be homozygous for a 2596T-C transition resulting in an ile841-to-thr substitution. Table 1 in their article had erroneously stated that the change occurred at position 843.)
.0004 BLOOM SYNDROME
In a patient with Bloom syndrome (210900), Foucault et al. (1997) identified compound heterozygosity for a 3181G-T transversion in the RECQL3 gene resulting in a cys1036-to-phe (C1036F) substitution in the C-terminal region of the peptide and an unidentified mutation affecting expression of the RECQL3 gene. The patient was initially believed to be homozygous for the C1036F mutation, but SSCP analysis, direct sequencing of RT-PCR products, and EcoRI digestion using a restriction site created by the mutation showed that the mutation was not present in low SCE cells from the patient. No EcoRI digestion was observed on paternal PCR products. Partial EcoRI digestion was seen with PCR products from maternal and patient DNA and from high- and low-SCE cells from the patient, and direct sequencing confirmed the presence of both a wildtype and mutated sequence at nucleotide 3181 in the high- and low-SCE cell lines, indicating heterozygosity for the mutation. Foucault et al. (1997) concluded that somatic intragenic recombination resulted in cells that had an untranscribed allele carrying the 2 parental RECQL3 mutations and a wildtype allele which allowed reversion to the low-SCE phenotype.
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